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PDBsum entry 2qo2
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Transferase PDB id
2qo2

 

 

 

 

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JSmol PyMol  
Contents
Protein chain
282 a.a. *
Ligands
BME
Waters ×335
* Residue conservation analysis
PDB id:
2qo2
Name: Transferase
Title: Human epha3 kinase and juxtamembrane region, dephosphorylated, apo structure
Structure: Ephrin receptor. Chain: a. Fragment: juxtamembrane segment and kinase domain: residues 577-947. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: placenta. Gene: epha3. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
1.60Å     R-factor:   0.177     R-free:   0.203
Authors: T.Davis,J.R.Walker,E.M.Newman,F.Mackenzie,C.Butler-Cole,J.Weigelt, M.Sundstrom,C.H.Arrowsmith,A.M.Edwards,A.Bochkarev,S.Dhe-Paganon, Structural Genomics Consortium (Sgc)
Key ref:
T.L.Davis et al. (2008). Autoregulation by the juxtamembrane region of the human ephrin receptor tyrosine kinase A3 (EphA3). Structure, 16, 873-884. PubMed id: 18547520 DOI: 10.1016/j.str.2008.03.008
Date:
19-Jul-07     Release date:   21-Aug-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P29320  (EPHA3_HUMAN) -  Ephrin type-A receptor 3 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		983 a.a.
282 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.2.7.10.1  - receptor protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
L-tyrosyl-[protein]
 + ATP
 = O-phospho-L-tyrosyl-[protein]
 + ADP
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1016/j.str.2008.03.008 Structure 16:873-884 (2008)
PubMed id: 18547520  
 
 
Autoregulation by the juxtamembrane region of the human ephrin receptor tyrosine kinase A3 (EphA3).
T.L.Davis, J.R.Walker, P.Loppnau, C.Butler-Cole, A.Allali-Hassani, S.Dhe-Paganon.
 
  ABSTRACT  
 
Ephrin receptors (Eph) affect cell shape and movement, unlike other receptor tyrosine kinases that directly affect proliferative pathways. The kinase domain of EphA3 is activated by ephrin binding and receptor oligomerization. This activation is associated with two tyrosines in the juxtamembrane region; these tyrosines are sites of autophosphorylation and interact with the active site of the kinase to modulate activity. This allosteric event has important implications both in terms of understanding signal transduction pathways mediated by Eph kinases as well as discovering specific therapeutic ligands for receptor kinases. In order to provide further details of the molecular mechanism through which the unphosphorylated juxtamembrane region blocks catalysis, we studied wild-type and site-specific mutants in detail. High-resolution structures of multiple states of EphA3 kinase with and without the juxtamembrane segment allowed us to map the coupled pathway of residues that connect the juxtamembrane segment, the activation loop, and the catalytic residues of the kinase domain. This highly conserved set of residues likely delineates a molecular recognition pathway for most of the Eph RTKs, helping to characterize the dynamic nature of these physiologically important enzymes.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Overall Structure of EphA3 Kinase
All molecular graphics figures were generated using PyMOL unless noted.
(A) Cartoon representation of the EphA3 JMKIN base ANP structure. The structure is shown in forest green and in cartoon representation. Secondary structure elements and regions discussed in the test are labeled. Regions of disorder are indicated with dashed lines. This structure was chosen because it represents the highest degree of order modeled for all the EphA3 structures.
(B) Ribbon representation of JMKIN base ANP overlaid with EphB2 in pink (1JPA). Alignment over all atoms yields an rmsd of less than 1Å for all structures; key regions of structural difference occur in the N-terminal lobe, centered on the JMS and the AL, along with slight differences in the β1-G loop-β2 region. 		Figure 4.
Figure 4. The Linker Between the Kinase and SAM Domains Binds into a Complementary Pocket on the C-terminal Lobe of the Kinase Domain
An electrostatic surface was generated using APBS (Baker et al., 2001) using a gradient from −10 to 10 keT. Shown in cartoon and stick representation is the model for KIN ANP in firebrick red; this model contains the most ordered linker region comprising residues 885–906. Highlighted is the complementary surface made up by Tyr841, Leu901, and Leu903.
 
  The above figures are reprinted by permission from Cell Press: Structure (2008, 16, 873-884) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21536040 G.De Lorenzo, A.Brutus, D.V.Savatin, F.Sicilia, and F.Cervone (2011).
Engineering plant resistance by constructing chimeric receptors that recognize damage-associated molecular patterns (DAMPs).
  FEBS Lett, 585, 1521-1528.  
21636893 G.Kisselman, W.Qiu, V.Romanov, C.M.Thompson, R.Lam, K.P.Battaile, E.F.Pai, and N.Y.Chirgadze (2011).
X-CHIP: an integrated platform for high-throughput protein crystallization and on-the-chip X-ray diffraction data collection.
  Acta Crystallogr D Biol Crystallogr, 67, 533-539.  
21439481 N.Singla, H.Erdjument-Bromage, J.P.Himanen, T.W.Muir, and D.B.Nikolov (2011).
A semisynthetic Eph receptor tyrosine kinase provides insight into ligand-induced kinase activation.
  Chem Biol, 18, 361-371.  
20697431 G.Shi, G.Yue, and R.Zhou (2010).
EphA3 functions are regulated by collaborating phosphotyrosine residues.
  Cell Res, 20, 1263-1275.  
20453867 H.E.Grecco, P.Roda-Navarro, A.Girod, J.Hou, T.Frahm, D.C.Truxius, R.Pepperkok, A.Squire, and P.I.Bastiaens (2010).
In situ analysis of tyrosine phosphorylation networks by FLIM on cell arrays.
  Nat Methods, 7, 467-472.  
20336692 M.Rabiller, M.Getlik, S.Klüter, A.Richters, S.Tückmantel, J.R.Simard, and D.Rauh (2010).
Proteus in the world of proteins: conformational changes in protein kinases.
  Arch Pharm (Weinheim), 343, 193-206.  
19658168 E.Stuttfeld, and K.Ballmer-Hofer (2009).
Structure and function of VEGF receptors.
  IUBMB Life, 61, 915-922.  
19823572 P.W.Janes, S.H.Wimmer-Kleikamp, A.S.Frangakis, K.Treble, B.Griesshaber, O.Sabet, M.Grabenbauer, A.Y.Ting, P.Saftig, P.I.Bastiaens, and M.Lackmann (2009).
Cytoplasmic relaxation of active Eph controls ephrin shedding by ADAM10.
  PLoS Biol, 7, e1000215.  
19678838 T.L.Davis, J.R.Walker, A.Allali-Hassani, S.A.Parker, B.E.Turk, and S.Dhe-Paganon (2009).
Structural recognition of an optimized substrate for the ephrin family of receptor tyrosine kinases.
  FEBS J, 276, 4395-4404.
PDB codes: 3fxx 3fy2
19028587 X.Huang, P.Finerty, J.R.Walker, C.Butler-Cole, M.Vedadi, M.Schapira, S.A.Parker, B.E.Turk, D.A.Thompson, and S.Dhe-Paganon (2009).
Structural insights into the inhibited states of the Mer receptor tyrosine kinase.
  J Struct Biol, 165, 88-96.
PDB codes: 2p0c 3bpr 3brb
19553108 Y.Choi, F.Syeda, J.R.Walker, P.J.Finerty, D.Cuerrier, A.Wojciechowski, Q.Liu, S.Dhe-Paganon, and N.S.Gray (2009).
Discovery and structural analysis of Eph receptor tyrosine kinase inhibitors.
  Bioorg Med Chem Lett, 19, 4467-4470.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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